Stanley N. Cohen Papers

Born in Perth Amboy, New Jersey February 17, 1935, Stanley Norman Cohen is Kwoh-Ting Li professor of genetics at Stanford University School of Medicine. Cohen and UC San Francisco scientist Herbert Boyer were the first scientists to transplant genes from one living organism to another and is often considered the birth of genetic engineering and DNA therapies. In addition to the medical advances produced by their work, the financial impact of the patents for the Boyer-Cohen processes to both Stanford and UCSF marked a shift in the way universities recognized the commercial value of their scientists and helped launch the nascent biotechnology industry. Cohen's DNA cloning research was the result of his interest in basic scientific inquiry into fundamental natural phenomena, not to create new tools for diagnosing human disease. This ethos and commitment to basic scientific research is a defining principle of Cohen's work.

Cohen was raised and educated in the Garden State. His broad range of intellectual curiosity, though not confined to academia, led to distinctive scholarly achievements at Perth Amboy High School and Rutgers University. In additional to his scientific skills, young Cohen was a successful debater, banjo and ukulele musician, and published pop music composer. After graduating from Rutgers Cohen shifted his scientific ambitions from physics to medicine and continued his studies at the University of Pennsylvania School of Medicine, where he graduated with a medical degree in 1960.

For the next seven years, Dr. Cohen held internships and fellowships at Mt. Sinai Hospital in New York City, University Hospital in Ann Arbor, Michigan, and Duke University Hospital in Durham, North Carolina, among other institutions. While at the National Institute for Arthritis and Metabolic Diseases he refocused his efforts toward a combination of basic research with clinical practice. As a post-doctoral researcher at the Albert Einstein College of Medicine in 1967 he taught while also studying the mechanisms which control gene expression.

Upon accepting a position with Stanford University in 1968, Dr. Cohen began experimenting with plasmids to understand the mechanisms that underlie antibiotic resistance. Plasmids are genetic elements within bacteria. They independently reproduce within bacteria molecules, generating drug resistance genes. As such, plasmids are an obvious starting point for studying how and why bacteria develop resistance to antibiotics. To do this work it was necessary to develop a way to pull plasmids apart, glue segments of them back together again, then propagate and clone new combinations of plasmid genes in living cells.

In collaboration with Norman Davidson and Phillip Sharp at Caltech, Dr. Cohen's lab initiated a plasmid study using electron microscopy. These investigations proved a link between bacterial DNA carried in plasmids and the formation of resistance-plasmid DNA.

A necessary next step in studying the molecular biology of plasmids was the reintroduction of plasmid DNA molecules into bacteria. By isolating drug resistant plasmid DNA and placing it into bacteria, the reaction could be studied. Specifically, one could learn whether new non-drug-resistant plasmids were produced. If such reproduction occurred, plasmid DNA could be a starting point for instigating the generation of large quantities of DNA in bacteria. Initially these investigations were hampered by the method of isolation and reintroduction.

Mechanical shearing broke apart plasmid molecules, producing fragmented plasmid DNA. Fragmented resistance plasmid DNA was put into bacteria and the reaction studied. Shearing proved too imprecise a method, fragments didn't cleanly interact, and the resulting insights were minimal.

A more precise method for cutting plasmid DNA molecules was introduced in 1970 which used enzymes. An endonuclease, or enzyme, is a protein that functions as a catalyst in regulating chemical reactions in an organism. It was found that certain endonucleases naturally cut up foreign DNA which may be present in bacteria. Called restriction endonucleases, endonucleases cut DNA in precise, site-specific locations, in a way that left "sticky" ends, which were ideally suited to bond with other DNA.

If a restriction endonuclease could be adapted to cut DNA within a plasmid and the resulting plasmid were reintroduced into bacteria and it reproduced, DNA, or genetic, cloning would be achieved; the process of inducing the production of genetically identical substances.

In 1972 Dr. Cohen began a collaboration with Dr. Herbert Boyer, of the University of California, San Francisco. Dr. Boyer had demonstrated the viability of a restriction endonuclease in E. Coli, known as EcoRI. Dr. Cohen used it to clone antibiotic resistance genes in plasmids. This innovative technique, known as recombinant DNA technology, was patented by Drs. Cohen and Boyer in 1980, one of the first biotechnology patents. Before its expiration in 1997, the patent issued 461 licenses.

Shortly after his initial success, Dr. Cohen combined staphylococcus aureus DNA and E. coli DNA in an experiment proving the hypothesis that interspecies cloning was possible. This demonstration raised fears about biohazard safety and ethical concerns over cloning technology in the scientific community. In 1975 the influential Asilomar Conference on Recombinant DNA conference organized by Paul Berg was held to discuss the potential biohazards and regulation of biotechnology. A group of about 140 professionals (primarily biologists, but also including lawyers and physicians) participated in the conference to draw up voluntary guidelines to ensure the safety of recombinant DNA technology. The U.S. government, in an attempt to regulate and develop formal policies for how to conduct DNA research, created the Recombinant DNA Advisory Committee which published the Recombinant DNA Research Guidelines in 1976. Cohen argued throughout these debates that recommended containment levels for certain types of research should be lowered on the grounds that there is little risk involved. In the ensuing decades recombinant DNA technology has enhanced substances in a variety of fields, including biotechnology, medicine, medical research, food production, agriculture, and industry, and has spawned the field of genomics. This field of research intentionally also served to bring scientific research more into the public domain.

Dr. Cohen's lab has long been interested in the evolution and dissemination of antibiotic resistance, and continues to pursue these interests by investigating the biology underlying the ability of bacteria to adapt non-mutationally to antibiotic exposure and other environmental stresses via the study of plasmid inheritance, cell growth, mobile genetic elements, cancers, viruses, toxins, and drug therapy. As of 2017 the lab's research interests include how expansion of gene regions containing nucleotide repeats (NRs) has a causal role in a variety of inherited degenerative neurological diseases, including Huntington's Disease, certain spinocerebellar ataxias and muscular dystrophies, and some types of amyotrophic lateral sclerosis and frontotemporal dementia. This involves the study of mechanisms that selectively enable transcription through expanded NR regions in human genes, actions of abnormal mRNAs and proteins generated by such repeats, and efforts at treating those diseases by targeting expression of the abnormal genes.

Lastly, Dr. Cohen was a primary figure in the establishment of collaborative research with the Institute of Molecular Biology in Taipei and in helping to establish a biotechnology industry in Taiwan. For his significant scientific contributions Cohen has received the Albert and Mary Lasker Award, the Wolf Foundation Prize, the Presidential Medal of Science, and election to the Inventors' Hall of Fame, among many other honors.